The idea that most of the human genome is transcribed dates back to the early 1970s. Workers isolated RNA from various sources and hybridized it to DNA (Rot analysis). They measured the amount of DNA that was complementary to this RNA and discovered two things:

Using highly purified messenger RNA (mRNA) the amount of DNA suggested that the genome had between 15,000 and 20,000 genes.

Using heterogeneous nuclear RNA (hnRNA) a much larger percentage of the genome was covered. This included the repetitive DNA fraction that we now know consist mostly of defective transposons.

These discoveries lead to intensive investigation of these non-coding DNA sequences and contributed to the discovery of introns and splicing. That accounted for a great deal of the mass of nuclear RNA that never made it into mature mRNA. Still, there was lots of RNA being synthesized that couldn't be accounted for. The data showed that this fraction was very complex (lot's of sequences) but that individual RNAs were not very abundant.

The main references quoted these days are Milcarek et al. (1974), Hugh et al. (1975), Holland et al. (1980), and Varley et al. (1980) but there were dozens of papers. The work was summarized in great detail in the first edition of Gene Expression by Benjamin Lewin. Most molecular biologists knew of these results.

Andyjones commented on this finding ...

... some people have known since the mid 70s that most DNA is transcribed into RNA, but sat on it because apparently they didn’t realise its significance ...

Now, to my mind the first point only underlines my original point about the cult of Darwinism (word defined according to the old-school, traditional and popular usage); that it can get in the way of the practice and dissemination of science, a dysteleological worldview which stagnates interest in trying to find function, something which has only recently been picked up again by ENCODE, and only then, Larry claims, because they don’t understand evolution.

It's true that most scientists were puzzled by this pervasive transcription but gradually they learned that a lot of it was introns and the rest was probably spurious transcription or junk RNA. They reached this conclusion because most of the transcripts were of very low abundance and were turned over (degraded) very rapidly.

I don't know where andyjones got the idea that scientist "sat on" the data. He seems to have made it up.

Andyjones says ....

The idea that (almost) everything gets transcribed sometimes but only by accident, is an explanation, but it is one that requires no investigation, and inspires no investigation. It is much more convincing to an already-convinced Darwinist than to anyone else. A Darwinist says, nah, there’s nothing here to be understood, stop looking. But to others, that would be a presumptuous ‘evolution-of-the-gaps’. Anyone who has reason to suspect teleology (meaning: engineering intent) is going to look just that little bit harder, and is going to see the importance of pervasive transcription just that little bit earlier.

Many scientists wanted to find a function for all of this RNA but they failed to do so. Meanwhile, other studies showed that much of our genome was probably junk DNA. This is about the time that scientists discovered pseudogenes (early 1980s) and discovered that half our genome was transposon pseudogenes (defective transposons). Experiments showed that a lot of pervasive transcription came from those regions of the genome suggesting that the transcripts were not functional.

It's simply not true to claim that the junk RNA explanation was not based on solid evidence and it's not true to claim that it stifled investigation. It's also ironic that andyjones thinks that the "Darwinists" would give up looking for an explanation when they (Darwinists) were doing the exact opposite! It's those who prefer natural selection (Darwinists) who most wanted there to be a function for this RNA. They still do.

I wonder if we should not be a little angry that this was not popularised in the 70s! My fiancee, who has a recent biology degree, is now annoyed that this fact was kept from her … The Darwinian establishment seem to have buried it, exactly the kind of thing I wanted to warn against.

The existence of hnRNA was widely known in the 1970s. It was discussed in graduate courses when I was a student. By the late 1970s we were teaching this material to undergraduates.

By 1990, the general consensus was that most of the rapidly degraded nuclear transcripts were probably introns although it was still an open question. That's the view that Benjamin Lewin popularized in his textbook Genes IV in 1990. The next decade showed that this was wrong because hundreds and hundreds of ESTs (expressed sequence tags) were being sequenced and most of them could not be assigned to a known gene.

35 comments:

Great post! So is the current consensus that rapidly degraded nuclear transcripts are mostly defective transposons? Since defective transposons were discovered in the early 1980s, why were they ignored in the 1990 consensus?

Then again, they probably all require a genetics course, and every genetics course these days must include at least a little bit about molecular evolution. But I doubt that most go into the level of detail we need here. The point is that there is no apparent conspiracy to hide the truth from andyjones' girlfriend.

Not necessarily. You can design a genetics course at pretty much any level of difficulty without ever touching molecular evolution. There are plenty of other things to talk about.

I have always wanted to take a formal class in molecular evolution. You can learn a lot on your own, and I have been filling the gaps in my education over the years by doing that, but there is no substitute for being in a well organized course taught by someone who really knows what he's talking about - there is very often important information "between the lines" that you may miss and that's best directly explained by an expert. But I have not been able to do so in either of the places where I've been at as undergraudate or a graduate student, for the simple reason there was no such course, and there was no such course because I don't think there was anyone to teach it. Unless you are at a large institution that covers a really broad range of biological fields, and let's say, you have a department of genetics, which has experts in molecular evolution in it, it is surprisingly easy to completely divorce molecular evolution from molecular biology and biochemistry education. You can spend all of your time learning about molecules, pathways, laboratory techniques, etc. and never be forced to or feel the need to learn about molecular evolution; and a lot of the people who are in those programs are premeds anyway which I would goes does figure in the decision making regarding what they should be required to take. Obviously, I am just speculating here based on what I have observed and seen - I don't know how programs are actually made - but I know I have not been forced to take such classes (and as I mentioned above, I couldn't take them even if I wanted to) and I don't know of anyone around me who has taken such courses as an undergrad.

Not only that, bur rvrn if you make a course in Molecular Evolution you have a lot of different ground that can be the focus of the course. For example, I did a course in ME and we did cover some generalities of genomics and comparative genomics but most of the focus was on evolutionary models at the sequence level. That leaves out most of the stuff relevant to this case. So taking a course in ME doesn't insure you'll necessarily cover stuff like pervasive transcription at all.

I'm pretty happy with the courses given at my University. We have optional courses on Genomics, Molecular Evolution, Molecular Systematics, Microbial Genomics, Pathogen Genomics, Viral Evolution and Molecular Epidemiology, etc and they are open to all levels of learning (bachelors, masters, post-graduates, etc).

But I have not been able to do so in either of the places where I've been at as undergraudate or a graduate student, for the simple reason there was no such course, and there was no such course because I don't think there was anyone to teach it.

I'm going to be in Los Angeles in June. Invite me to your lab and I'll be happy to give you the short version. I'll even throw in a free lecture on the evidence for junk DNA!

I doubt that every undergraduate biology degree, even these days, requires even one course in molecular evolution.

Every life sciences program should require a course on evolution in first year. That course MUST include some basic population genetics and it MUST cover Neutral Theory and the fundamentals of molecular evolution. That's how you have to teach evolution these days.

Every life sciences program MUST require an introductory biochemistry/molecular biology course—in second (sophomore) year. This is the 21st century and it would be absurd to make biochemistry/molecular biology optional or allow it to be put off until fourth (senior) year. The biochemistry course should explain how to compare amino acid sequences and how to interpret this in terms of molecular evolution.

I'm going to be in Los Angeles in June. Invite me to your lab and I'll be happy to give you the short version. I'll even throw in a free lecture on the evidence for junk DNA!

You're certainly welcome as far as I am concerned though I am not exactly the one who send invitations. We do know about junk DNA though, I can assure you of that.

Also, when I said I have gaps in my education to fill in, I did not mean the kind of gaps that can be filled with a short talk but rather the ones that you need to spend quite a bit of time focused on the subject to truly go in depth. Which is not that easy to do when you also have a lot of research to do.

Which, BTW, is a main reason for the problem - obviously I am not in a position to make sweeping generalizations about biomedical research, but it seems to me that the majority of people are so occupied with their own research that they have very little time to learn about things not directly related to it. Combine that with the fact that making sure students have an understanding of molecular evolution is not a mandatory component of most undergraduate programs, which we discussed above, and with the fact that a lot of people enter biology from other fields (physics, computer science, chemistry, etc) and such people most certainly were not exposed to those concepts, and you can easily see how the current situation came to be.

There is always a conspiracy afoot. Not to derail into the political...but what is it with conservatives?

Whatever researchers might have gathered in earlier decades of molecular biology, it was still a suspicion in many minds that it would take many more than 25K genes to make something as complex as a human. Thus, if wide-spread transcription was noted..it would hardly be something that scientists would "sit on" or try to suppress for conspiratorial reasons. A hundred thousand genes in the human genome, were it so, would hardly be an embarrassment to the "cult of Darwin" or disprove evolution in any way. Likewise, I don't understand why IDers feel it is necessary that the human genome must have more than 25K genes for the sake of their idea. Doesn't god move in mysterious ways, after all?

Heh, one might even say it would be more impressive if god made more with less.

Did I say god? Bleargh, I meant an unnamed designer who's been alive for at least billions of years, seemingly unaffected by multiple extinction events, and can reach into the genomes of all organisms on the planet (and probably beyond) at will and steer and guide around mutations and molecules.

Thus, if wide-spread transcription was noted..it would hardly be something that scientists would "sit on" or try to suppress for conspiratorial reasons.

I call this "Accusation of Concealment." Accusation of Concealment is central to all anti-evolution arguments.

Remember, creationists address themselves to non-scientist audiences, who don't know obscure [to muggles] details of science. So it is very easy, in every branch of science, for creationists to relate to their non-scientist audience some scientific point that is obscure to muggles but very well-known among scientists, and then say, "Why have you never heard about this? Because scientists CONCEALED it!"

My favorite example of "Accusation of Concealment" is when a creationist says that scientists CONCEALED the fact "saurischian" [referring to dinosaurs like Tyrannosaurus] means "lizard-hipped", but "ornithischian" [referring to dinosaurs like apatosaurus] means "bird-hipped", yet scientists think that birds evolved from saurischian dinosaurs, due to the convergent evolution of the reversed pubic bone in birds and ornithischians.

So some creationist learned the meaning of the word "ornithischian" and upon learning something new, immediately thought, "The Scientists have CONCEALED the meaning of this Latin word! I must inform the non-Latin-speaking people that scientists LIED to them!"

Of course, last time I was in the AMNH in New York City, they had a huge kiosk in the MIDDLE of the aisle of their dinosaur exhibit, explaining the meaning of ornithtischian and saurischian, and saying that birds evolved from saurischian, not ornithischian, dinosaurs. The kiosk was so huge no one could miss it. I fell they were shoving this point down my throat.

Yes, people are always getting funding for research and then 'sitting on' the results because they are inconvenient to the Grand Darwinist Consensus in some way they barely comprehend themselves, not being evolutionary theorists.

Not to mention how all this Darwinian Speculation(tm) is stifling research everywhere, when they're the same people who's doing the research in the first place. Oh man, such a great hinderance to science they are, doing all the work and then just "sitting on it" by... publishing their results for others to replicate.

Even more strange how little(none, actually) genetics research is emerging out of creationist and ID "laboratories", and how little they publish in their "journals". How many functional elements have been experimentally confirmed in ID and Creationist journals? That's right. None.

Of course, they sure like to write a lot of books criticizing other people's work for not coming up with conclusions they like. I guess that's why the biologic institute bought so many computers for their "labs" instead of stuff like sequencing and pcr machines and all that actual lab-work related stuff.

Rumraket: Of course, they sure like to write a lot of books criticizing other people's work for not coming up with conclusions they like. I guess that's why the biologic institute bought so many computers for their "labs" instead of stuff like sequencing and pcr machines and all that actual lab-work related stuff.

I wouldn't put "labs" in scare quotes-- they do seem to have a real lab.

Do you have a link showing that they buy a disproportionate number of computers vs. lab equipment?

I'll see if I can dig it up. I remember there was a post about it somewhere on panda's thumb where their expenditures could be seen because someone had used one of those tax laws(don't remember the terminology here, not familiar with US tax and legal matters) to requiest some insight. In any case, it turned out that they apparently spend most of they money buying new fancy apple computers instead of actual lab equipment, and that this had been going on for a while.

Yes, I know they have an actualy lab. But what has emerged from this? I only remember one single study they did, where they tried to convert one modern enzyme into another modern enzyme through artificial selection. Then upon discovering this took multiple mutations that would destroy the function in the mean time, they concluded evolution could not produce new enzymes(neglecting to test the actual evolutionary account of the two specific enzymes from the common ancestor, instead of trying to directly convert one into the other).

And hey, we all remember that interview that was conducted at one point, where upon it becoming clear that they had actually found a beneficial mutation in, they shut down the interview. They've been doing some damage control on that account since that time(ignoring the whole thing about the mutation, choosing instead to focus on the manner in which the conversation surrounding the interview took place). Hilarious.

No, really... what do they do at that lab, other than construct intentioal strawmen of evolution to test once every 3 years?

My first reaction was amusement, but that quickly turned to outrage. Doug Axe pays himself $95,000 for doing what, exactly?

The working life of a university academic has been one of the ongoing themes of this blog, so readers here probably have a reasonable idea of how that figure compares to a typical university salary, not to mention the 40 hour work week, without having to prepare or deliver lectures, mark papers and the various other tasks entailed in academic life. I bet that's the cleanest freezer in America, what with all the time Axe has to keep it that way.

Wikipedia: Ahmanson is reported to have "never supported his mentor's calls for the death penalty for homosexuals";[7] instead, as the Orange County Register reported in 2004, he "no longer consider[s] [it] essential" to stone people who are deemed to have committed certain immoral acts. Ahmanson also told the Register, "It would still be a little hard to say that if one stumbled on a country that was doing that, that it is inherently immoral, to stone people for these things. But I don't think it's at all a necessity."[11]

What's really scary is that many people look up to Ahmanson as a hero who's fighting the good fight.

There is something that gives me some pleasure though. The guy is a billionaire yet he apparently can't think of anything better to do than worrying about how other people have sex. Big money, very small mind.

A salary of $95,000 is about the starting salary for an assistant professor of biochemistry in a medical schhol at a mid- rank research university.

I thought it was in that ballpark. Of course, you have to consider what is required to obtain and hold such a position. I don't think it would cut it if you performed absolutely no teaching activities, and your publications mainly consisted of the occasional blog post and a few articles in the department newsletter (AKA "BIO-Complexity"). It wouldn't matter how clean you kept the freezer.

There is something that gives me some pleasure though. The guy is a billionaire yet he apparently can't think of anything better to do than worrying about how other people have sex. Big money, very small mind.

Which is exactly why, in more civilized countries, people like him are taxed up the whazoo so their surplus income can actually be used for pro-social purposes, rather than to undermine scientific education.

Late to the party but the problem here is as much a failure to understand chemistry. Enzymes show remarkable specificity so people forget about a few or fractional percents. Somewhere students may have had to run a synthetic reaction and calculate a yield but have not adequately understood why they did not get 100%. Molecules don't read textbooks.

e^(-deltaG/RT) needs to be pounded home, repeatedly.

Your DNA binding post does this well. I'd reinforce it from other perspectives like this on protease specificity: http://www.ncbi.nlm.nih.gov/pubmed/15705970

Biochemistry is incapable of perfect specificity. And high specificity has its own cost in slowing kinetics for off rates any situation where binding must be reversible. That lesson is not being taught well enough. It's critical for when the thinking starts.

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Principles of Biochemistry 5th edition

Disclaimer

Some readers of this blog may be under the impression that my personal opinions represent the official position of Canada, the Province of Ontario, the City of Toronto, the University of Toronto, the Faculty of Medicine, or the Department of Biochemistry. All of these institutions, plus every single one of my colleagues, students, friends, and relatives, want you to know that I do not speak for them. You should also know that they don't speak for me.

Superstition

Quotations

The old argument of design in nature, as given by Paley, which formerlyseemed to me to be so conclusive, fails, now that the law of natural selection has been discovered. We can no longer argue that, for instance, the beautiful hinge of a bivalve shell must have been made by an intelligent being, like the hinge of a door by man. There seems to be no more design in the variability of organic beings and in the action of natural selection, than in the course which the wind blows.

Charles Darwin (c1880)Although I am fully convinced of the truth of the views given in this volume, I by no means expect to convince experienced naturalists whose minds are stocked with a multitude of facts all viewed, during a long course of years, from a point of view directly opposite to mine. It is so easy to hide our ignorance under such expressions as "plan of creation," "unity of design," etc., and to think that we give an explanation when we only restate a fact. Any one whose disposition leads him to attach more weight to unexplained difficulties than to the explanation of a certain number of facts will certainly reject the theory.

Charles Darwin (1859)Science reveals where religion conceals. Where religion purports to explain, it actually resorts to tautology. To assert that "God did it" is no more than an admission of ignorance dressed deceitfully as an explanation...

Quotations

I have championed contingency, and will continue to do so, because its large realm and legitimate claims have been so poorly attended by evolutionary scientists who cannot discern the beat of this different drummer while their brains and ears remain tuned to only the sounds of general theory.

The essence of Darwinism lies in its claim that natural selection creates the fit. Variation is ubiquitous and random in direction. It supplies raw material only. Natural selection directs the course of evolutionary change.

Rudyard Kipling asked how the leopard got its spots, the rhino its wrinkled skin. He called his answers "just-so stories." When evolutionists try to explain form and behavior, they also tell just-so stories—and the agent is natural selection. Virtuosity in invention replaces testability as the criterion for acceptance.

The first commandment for all versions of NOMA might be summarized by stating: "Thou shalt not mix the magisteria by claiming that God directly ordains important events in the history of nature by special interference knowable only through revelation and not accessible to science." In common parlance, we refer to such special interference as "miracle"—operationally defined as a unique and temporary suspension of natural law to reorder the facts of nature by divine fiat.

Quotations

My own view is that conclusions about the evolution of human behavior should be based on research at least as rigorous as that used in studying nonhuman animals. And if you read the animal behavior journals, you'll see that this requirement sets the bar pretty high, so that many assertions about evolutionary psychology sink without a trace.

Jerry Coyne
Why Evolution Is TrueI once made the remark that two things disappeared in 1990: one was communism, the other was biochemistry and that only one of them should be allowed to come back.

Sydney Brenner
TIBS Dec. 2000
It is naïve to think that if a species' environment changes the species must adapt or else become extinct.... Just as a changed environment need not set in motion selection for new adaptations, new adaptations may evolve in an unchanging environment if new mutations arise that are superior to any pre-existing variations

Douglas Futuyma
One of the most frightening things in the Western world, and in this country in particular, is the number of people who believe in things that are scientifically false. If someone tells me that the earth is less than 10,000 years old, in my opinion he should see a psychiatrist.

Francis Crick
There will be no difficulty in computers being adapted to biology. There will be luddites. But they will be buried.

Sydney Brenner
An atheist before Darwin could have said, following Hume: 'I have no explanation for complex biological design. All I know is that God isn't a good explanation, so we must wait and hope that somebody comes up with a better one.' I can't help feeling that such a position, though logically sound, would have left one feeling pretty unsatisfied, and that although atheism might have been logically tenable before Darwin, Darwin made it possible to be an intellectually fulfilled atheist

Richard Dawkins
Another curious aspect of the theory of evolution is that everybody thinks he understand it. I mean philosophers, social scientists, and so on. While in fact very few people understand it, actually as it stands, even as it stood when Darwin expressed it, and even less as we now may be able to understand it in biology.

Jacques Monod
The false view of evolution as a process of global optimizing has been applied literally by engineers who, taken in by a mistaken metaphor, have attempted to find globally optimal solutions to design problems by writing programs that model evolution by natural selection.